Potential kidney protection with liraglutide and semaglutide: Exploratory mediation analysis
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Dokumenter
- Fulltext
Forlagets udgivne version, 1,64 MB, PDF-dokument
Aims: To investigate whether effects on chronic kidney disease risk factors could explain the apparent reduction in kidney outcomes (composite of macroalbuminuria, doubling of serum creatinine, renal replacement therapy, or renal death), primarily driven by changes in albuminuria, after treatment with the glucagon-like peptide-1 receptor agonists (GLP-1RAs) liraglutide and semaglutide in patients with type 2 diabetes in the LEADER and SUSTAIN 6 trials. Materials and Methods: We evaluated the mediation effect of glycated haemoglobin (HbA1c), systolic blood pressure (BP), and body weight on the kidney effects of GLP-1RAs. Diastolic BP, haemoglobin, heart rate, low-density lipoprotein and total cholesterol, and white blood cell count were also investigated. The mediation effect was estimated by the novel Vansteelandt statistical method. Subgroups with estimated glomerular filtration rate (eGFR) <60 and ≥60 mL/min/1.73 m2 were examined in LEADER. Results: We observed that HbA1c mediated 25% (95% confidence interval [CI] −7.1; 67.3) and 26% (95% CI noncalculable), and systolic BP 9% (95% CI 2.8; 22.7) and 22% (95% CI noncalculable) of kidney effects of GLP-1RAs in LEADER and SUSTAIN 6, respectively. Small or no mediation was observed for the other parameters; for example, body weight mediated 9% (95% CI −7.9; 35.5) in the former and did not mediate effects in the latter study. Mediation by HbA1c was greater in patients with eGFR ≥60 mL/min/1.73 m2 (57%) versus those with eGFR <60 mL/min/1.73 m2 (no mediation). Conclusions: Our results suggest that HbA1c and systolic BP may moderately mediate kidney benefits of liraglutide and semaglutide, with all other variables having a small to no effect. Potential kidney benefits may be driven by other mediators or potentially by direct mechanisms.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Diabetes, Obesity and Metabolism |
| Vol/bind | 23 |
| Udgave nummer | 9 |
| Sider (fra-til) | 2058-2066 |
| Antal sider | 9 |
| ISSN | 1462-8902 |
| DOI | |
| Status | Udgivet - 2021 |
Bibliografisk note
Funding Information:
LEADER, SUSTAIN 6 and the present analysis were funded by Novo Nordisk A/S. The authors thank all trial personnel and participants, and Sonia Vyskocilova, PhD, and Izabel James, MBBS, of Watermeadow Medical, an Ashfield company (funded by Novo Nordisk A/S), for medical writing and editorial assistance. Parts of the data included here have been published as an abstract and presented as an oral presentation at the American Society of Nephrology Kidney Week in 2019 ( 2019; 30:SA OR082), and at the European Association for the Study of Diabetes virtual meeting on September 23, 2020 (abstract 134). J Am Soc Nephrol
Funding Information:
LEADER, SUSTAIN 6 and the present analysis were funded by Novo Nordisk A/S. The authors thank all trial personnel and participants, and Sonia Vyskocilova, PhD, and Izabel James, MBBS, of Watermeadow Medical, an Ashfield company (funded by Novo Nordisk A/S), for medical writing and editorial assistance. Parts of the data included here have been published as an abstract and presented as an oral presentation at the American Society of Nephrology Kidney Week in 2019 (J Am Soc Nephrol 2019; 30:SA OR082), and at the European Association for the Study of Diabetes virtual meeting on September 23, 2020 (abstract 134).
Funding Information:
J.F.E.M. has received speaker honoraria from Astra, Boehringer Ingelheim, Eli Lilly & Co, Medice, Novo Nordisk, Roche, and Vifor Pharma, research support from the European Union, Canadian Institutes of Health Research, Astra, Boehringer Ingelheim, Novo Nordisk, Roche and Sandoz, and consultation fees from Astra, Bayer, Novo Nordisk and Vifor Pharma. J.B.B.'s contracted consulting fees and travel support for contracted activities are paid to the University of North Carolina by Adocia, AstraZeneca, Dance Biopharm, Eli Lilly, Fortress Biotech, MannKind, NovaTarg, Novo Nordisk, Sanofi, Senseonics, vTv Therapeutics and Zafgen, as well as grant support from NovaTarg, Novo Nordisk, Sanofi, Tolerion and vTv Therapeutics. J.B.B. is also a consultant to Cirius Therapeutics Inc, CSL Behring, Fortress Biotech, Mellitus Health, Neurimmune AG, Pendulum Therapeutics, Stability Health and Zealand Pharma, holds stock/options in Mellitus Health, Pendulum Therapeutics, PhaseBio and Stability Health, and is supported by grants from the National Institutes of Health in part for this effort (UL1TR002489, P30DK124723). T.I. is an employee of Novo Nordisk and a significant stockholder. L.A.L. has received honoraria for advisory board participation from, and has provided continuing medical education on behalf of, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk, Sanofi and Servier, and has received research grants from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Janssen, Lexicon, Novo Nordisk and Sanofi. R.E.P. has received research grants from Gilead Sciences, Lexicon Pharmaceuticals, Ligand Pharmaceuticals Inc., Lilly, Merck, Novo Nordisk, Sanofi‐Aventis US LLC, and Takeda, has acted as a speaker for AstraZeneca, Novo Nordisk and Takeda, and as a consultant for AstraZeneca, Boehringer Ingelheim, Eisai, Inc., GlaxoSmithKline, Janssen Scientific Affairs LLC, Ligand Pharmaceuticals Inc., Lilly, Merck, Novo Nordisk, Pfizer and Takeda. All payments are made directly to his employer (AdventHealth). S.R. is a Novo Nordisk employee and stockholder. T.V. has served on scientific advisory panels, been part of speaker's bureaus for, served as a consultant to, and/or received research support from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Gilead, Mundipharma, MSD/Merck, Novo Nordisk, Sanofi and Sun Pharmaceuticals. B.W. is a Novo Nordisk employee and stockholder. V.P. has participated in steering committees, advisory boards, and/or received honoraria and consultation fees from Amgen, Janssen, GlaxoSmithKline, Astellas, Boehringer Ingelheim, Baxter, Mitsubishi Tanabe, Mundipharma, Retrophin, Merck, Abbvie, Novo Nordisk, AstraZeneca, Gilead, Durect, Servier, Tricida, Novartis, Eli Lilly, Relypsa, Pharmalink, Bayer and Bristol‐Myers Squibb.
Publisher Copyright:
© 2021 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.
ID: 304483151